PATENT BLUE V

העדוה העדוה

לע לע

הרמחה הרמחה

עדימ עדימ

)תוחיטב )תוחיטב :ךיראת

01.1.13

םש

רישכת

:תילגנאב

Patent Blue V

רפסמ

:םושיר

060-28-27291-05

םש

לעב

:םושירה

Promedico LTD

םייונישה

ןולעב

םינמוסמ

לע

עקר

בוהצ אפורל ןולעב אפורל ןולעב

םיטרפ

לע

םי/יונישה

םי/שקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

4.1 Therapeutic

indications

Marking lymph vessels and arterial regions.

Marking sentinel nodes before biopsy in patients with operable breast

cancer.

This medicinal product is for diagnostic use only.

Marking lymph vessels and arterial regions.

Marking sentinel nodes before biopsy in patients with operable breast cancer.

4.6 pregnancy and

lactation

Consequently, the use of this medicinal product is not recommended

during pregnancy.

Pregnancy

No reliable animal teratogenesis data are available.

There are no or limited amount of data from the use of Patent Blue V

in pregnant women.

Consequently, the use of Patent Blue V is not recommended during

pregnancy.

Lactation

It is unknown whether Patent Blue V is excreted in human milk.

Pregnancy

No reliable animal teratogenesis data are available.

Currently, there are no, or limited data, to evaluate a possible malformative or

foetotoxic effect of Patent Blue V when it is administered during pregnancy.

Consequently, the use of this medicinal product is not recommended during pregnancy.

Lactation

There are no data concerning excretion of Patent Blue V into breast milk.

4.8 Undesirable

effects

Immediate hypersensitivity reactions (several minutes to several

hours): urticaria is common, angioneurotic oedema and anaphylactic

shock are uncommon.

A bluish colouring of the integuments is observed after the injection,

which disappears within 24 to 48 hours. In patients with lymph stasis

or circulatory disorders, the colouring may last longer.

Immediate hypersensitivity reactions can occur. These reactions may comprise one or

more of the following effects, either concomitantly or successively: skin, respiratory

and/or cardiovascular reactions. Each of these effects can be a precursor sign of

anaphylactic shock.

A bluish discolouration of the integuments is observed after injection, which resolves

over the following 24 to 48 hours. The discolouration can persist for longer in the event

of lymph stasis or circulatory disorders.

Undesirable effects are given in the table below by System Organ Class and by

frequency, using the following classifications: very commom (≥1/10), common (≥1/100

to 1<1/10), uncommon (≥1/1,000 to 1<1/100), rare (≥1/10,000 to <1/1,000), very rare

(<1/10,000), unknown (cannot be estimated from available data).

System Organ Class

Frequency: adverse event

Immune system disorders

Unknown frequency: anaphylactic shock,

hypersensitivity

Skin and subcutaneous tissue disorders

Unkown frequency: angio-oedema,

urticaria, blue discolouration of the skin

General disorders and administration

site conditions

Unknown frequency: discolouration of

the administration site

5.3 Preclinical safety

data

Preclinical data derived from conventional single-dose and repeated-

dose safety pharmacology and toxicology studies have not revealed

any particular risk for humans.

Preclinical data derived from conventional single-dose and repeated-dose safety

pharmacology and toxicology studies have not revealed any particular risk for humans.

A mutagenic effect was observed in vitro, at high concentrations, on a bacterial gene

mutation test after metabolic activation. This effect was not confirmed on an in vitro

gene mutation test on mammalian cells (L5178Y murine lymphoma cells), or on a

micronucleus test in rats by intravenous injection of doses significantly higher than the

maximum dose in humans, and therefore has limited clinical significance.

ל ןולעב ל ןולעב ןכרצ ןכרצ םי/שקובמה םי/יונישה לע םיטרפ ןולעב קרפ יחכונ טסקט שדח טסקט ובש ,ןולעה

םינמוסמ

םייונישה

םישקובמה

לע

עקר

בוהצ

רבעוה

ראודב

ינורטקלא

ךיראתב

19.11.2012

םייק

ןולע

ןכרצ

אוהו

ןכדועמ

.םאתהב

אתכמסא

:השקבל

לש

ןרציה

יונישה

ל"נה

שגוה

תויושרל

תואירבה

תפרצב

חקורה ,ינא

הנוממה

לש

תרבח

Promedico LTD

ריהצמ

הזב

יכ

ןיא

םייוניש

םיפסונ

.ןולעב

תמיתח

חקורה

הנוממה

SUMMARY OF PRODUCT CHARACHTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

PATENT BLUE V

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

PATENT BLUE V SODIUM ....................................................................................... 2.50 g

per 100 ml of solution for injection

For a full list of excipients, see Section 6.1.

3.

PHARMACEUTICAL FORM

Solution for injection

4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications

This medicinal product is for diagnostic use only.

Marking lymph vessels and arterial regions.

Marking sentinel nodes before biopsy in patients with operable breast cancer.

4.2.

Posology and method of administration

Marking arterial regions: not more than 10 ml intra-arterially

Marking lymph vessels and the sentinel node: 1 to 2 ml subcutaneously around the tumour or areola.

4.3.

Contraindications

Hypersensitivity to Patent Blue V, to any of the excipients or to triphenylmethane dyes.

This medicinal product is generally not recommended during pregnancy.

4.4.

Special warnings and precautions for use

There is always a risk of hypersensitivity regardless of the route of administration and the dose administered.

Patent Blue V can induce minor or major, possibly life-threatening immediate hypersensitivity reactions that

can sometimes be fatal (anaphylactic shock). These reactions are often unpredictable, but occur more

frequently in patients with a history of hypersensitivity reaction to Patent Blue V or triphenylmethane dyes

contained in medicinal products, foods and cosmetics.

The indication for use of Patent Blue V must therefore be carefully evaluated in these predisposed patients.

Corticosteroids and H1 antihistamines have been proposed as premedication in patients at greatest risk of

hypersensitivity reactions (history of hypersensitivity to Patent Blue V or other triphenylmethane dyes).

However, this premedication does not exclude the possibility of serious or fatal anaphylactic shock.

Due to the risk of major hypersensitivity reactions, resuscitation equipment must be immediately at hand,

especially for patients on beta-blockers, in whom adrenaline and intravascular infusions may be less

effective. Consequently, Patent Blue V must be administered only in a setting able to adequately treat these

major hypersensitivity reactions.

Before administering Patent Blue V:

Identify high-risk subjects by means of a detailed clinical interview concerning the patient’s history;

Insert a venous catheter.

During the examination, ensure:

Medical surveillance;

Maintenance of a venous line;

That resuscitation equipment and medications are immediately at hand.

After administration of Patent Blue V, the patient must be kept under observation for at least 60 minutes.

In the event of an allergic reaction, an investigation must be conducted to determine whether, among all of

the medicinal products used during a surgical procedure with general anaesthesia, this reaction can be truly

attributed to Patent Blue V. The result of this investigation is important when another surgical procedure is

required (e.g. contralateral cancer).

All the team managing the patient must be trained in the sentinel node identification technique.

Data of the literature demonstrate improvement of the sentinel node identification rate by performing double

detection with a radiopharmaceutical and a dye.

4.5.

Interaction with other medicinal products and other forms of interaction

Medicinal products

Beta-blockers,

vasoactive

substances,

angiotensin-converting

enzyme

inhibitors,

angiotensin

receptor antagonists.

These medicinal products decrease the efficacy of cardiovascular mechanisms of compensation of blood

pressure disorders: the physician must be informed before injecting Patent Blue and resuscitation equipment

must be immediately at hand.

Other forms of interaction

The partial pressure of oxygen measured by spectrophotometry can be transiently and falsely lowered by

about 5 to 10% of baseline values, following an examination with Patent Blue V. When in doubt, arterial

blood gases should be checked. Methaemoglobinaemia, measured by the same spectrophotometric method,

can be falsely raised.

4.6.

Pregnancy and lactation

Pregnancy

No reliable animal teratogenesis data are available.

Currently, there are no, or limited data, to evaluate a possible malformative or foetotoxic effect of Patent Blue

V when it is administered during pregnancy.

Consequently, the use of this medicinal product is not recommended during pregnancy.

Lactation

There are no data concerning excretion of Patent Blue V into breast milk.

4.7.

Effects on ability to drive and use machines

The potential effects of Patent Blue V on the ability to drive and use machines have not been studied.

4.8.

Undesirable effects

Immediate hypersensitivity reactions can occur. These reactions may comprise one or more of the following

effects, either concomitantly or successively: skin, respiratory and/or cardiovascular reactions. Each of these

effects can be a precursor sign of anaphylactic shock.

bluish

discoloration of the

integuments

is observed after injection, which resolves over the following 24 to

48 hours. The discoloration can persist for longer in the event of lymph stasis or circulatory disorders.

Undesirable effects are given in the table below by System Organ Class and by frequency, using the

following classifications: very commom (

1/10), common (

1/100 to 1

<

1/10), uncommon (

1/1,000 to

<

1/100), rare (

1/10,000 to

<

1/1,000), very rare (

<

1/10,000), unknown (cannot be estimated from available

data).

System Organ Class

Frequency: adverse event

Immune system disorders

Unknown frequency: anaphylactic shock,

hypersensitivity

Skin and subcutaneous tissue disorders

Unkown frequency: angio-oedema, urticaria, blue

discolouration of the skin

General disorders and administration site conditions

Unknown frequency: discolouration of the

administration site

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows

continued monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the National

Regulation by using an online form

http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.

gov.il

and emailed to the Registration Holder’s Patient Safety Unit at:

drugsafety@neopharmgroup.com

4.9.

Overdose

No case of overdose has been reported to date.

5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic properties

Pharmacotherapeutic group:

Dye for vascular marking, ATC code: V04CX

5.2.

Pharmacokinetic properties

The dye is excreted within 24 to 48 hours, mainly in the urine, which is intensely stained, but also in the bile.

5.3.

Preclinical safety data

Preclinical data derived from conventional single-dose and repeated-dose safety pharmacology and

toxicology studies have not revealed any particular risk for humans.

A mutagenic effect was observed in vitro, at high concentrations, on a bacterial gene mutation test after

metabolic activation. This effect was not confirmed on an in vitro gene mutation test on mammalian cells

(L5178Y murine lymphoma cells), or on a micronucleus test in rats by intravenous injection of doses

significantly higher than the maximum dose in humans, and therefore has limited clinical significance.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of excipients

Sodium chloride, sodium phosphate dibasic, water for injection

6.2.

Incompatibilities

Not applicable.

6.3.

Shelf life

The expiry date of the product is indicated on the packaging materials.

6.4.

Special precautions for storage

Store

below

30°C protected from light.

6.5.

Nature and contents of container

2 mL type I colorless glass vial/ampoule.

6.6.

Special precautions for handling and disposal

Any unused medicinal product or waste material should be disposed of in accordance with local

requirements.

7. MANUFACTURER

Guerbet, France

BP 57400

95943 Roissy Charles De Gaulle cedex

France

8. MARKETING AUTHORISATION NUMBER(S)

060-28-27291-05

9. REGISTRATION HOLDER

Promedico Ltd,

P.O.Box 3340, Petach-Tiqva.

The format of this leaflet has been determined by the MOH and its content has been

checked and approved- December 2017.